In Cappadocia, Turkey, there are three villages, Karain, Old Sarihidir, and Tuzkoy, where 50% of deaths are[unreadable] caused by malignant mesothelioma (MM). This incredible epidemic has been linked to exposure to erionite,[unreadable] a type of zeolite fiber. We have established that genetic predisposition plays an important role in this MM[unreadable] epidemics. Our preliminary results demonstrate that in these villages, MM occurs prevalently in certain[unreadable] families and not in others, that'when high-risk MM family members marry into a low risk family, MM appears[unreadable] in the descendents. This finding indicates that genetics play a determining role in this epidemic. However,[unreadable] we also found that MM does not appear to develop in high risk family members born and raised outside[unreadable] these villages. This application is built around the central hypothesis that the epidemic of MM[unreadable] observed in Karain, Tuzkoy and "Old" Sarihidir is caused by the interaction of the environmental[unreadable] carcinogen erionite with genetic predisposition. 'Our hypothesis is that the same gene that is mutated[unreadable] in these Cappadocian families, is the main target of asbestos -and possibly SV40- carcinogenesis in[unreadable] sporadic MM in the Western world. We propose to try to identify the gene/s that predispose to MM in[unreadable] Cappadocia. We also propose to test the hypothesis that the erionite found in these villages has some[unreadable] unique characteristic that makes it more oncogenic compared to the erionite found in Nevada, Oregon,[unreadable] California, and in other parts of the world or to the erionite found in other Cappadocian villages with low or[unreadable] no prevalence of MM. Finally, we will test - in two American MM families we recently identifed - the[unreadable] hypothesis that the same gene that predispose to MM in Cappadocia, contributes to familial MM in the[unreadable] Western world. These studies will be facilitated by the interaction of a multidisciplinary team coordinated by[unreadable] Dr. Carbone, that includes Drs. Baris and Emri (Turkish physicians), Mossman (in vitro mechanistic[unreadable] studies), Testa (array-CGH), Cox (genetic linkage), Steele and Dogan (mineralogy), Pass (Clinical Core).